Positive CHMP Opinion for Datopotamab Deruxtecan (Datroway) for the treatment of unresectable or metastatic hormone receptor (HR)-positive, HER2-negative breast cancer
On 30 January 2025, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for the medicinal product Datroway, intended for the treatment of breast cancer. The applicant for this medicinal product is Daiichi Sankyo Europe GmbH.
Datroway will be available as a 100 mg powder for concentrate for solution for infusion. The active substance of Datroway is datopotamab deruxtecan, an antineoplastic agent (ATC code: L01FX35). Datopotomab deruxtecan is a monoclonal antibody-drug conjugate that binds to TROP2-expressing tumour cells and undergoes internalisation and intracellular cleavage. This results in the release of deruxtecan in target cells, which causes DNA damage and apoptotic cell death.
The benefit of Datroway is prolonged survival without disease progression compared to chemotherapy, as shown in a phase 3 randomised open-label study in patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-negative breast cancer, following one or two prior lines of systemic therapy.
The most common side effects are stomatitis, nausea, fatigue, alopecia, constipation, vomiting, dry eye, keratitis, anaemia, decreased appetite, increased aspartate transferase (AST), rash, diarrhoea, neutropenia and increased alanine aminotransferase (ALT).
The full indication is:
Datroway as monotherapy is indicated for the treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-negative breast cancer who have received endocrine therapy and at least one line of chemotherapy in the advanced setting (see section 5.1).
The positive opinion was based on findings from the phase 3 TROPION-Breast01 study (NCT05104866) in which the antibody-drug conjugate (ADC; n = 365) led to a median progression-free survival (PFS) of 6.9 months (95% CI, 5.7-7.4) by blinded independent central review (BICR) vs 4.9 months (95% CI, 4.2-5.5) with investigator’s choice of chemotherapy (n = 367), translating to a 37% reduction in the risk of disease progression or death (HR, 0.63; 95% CI, 0.52-0.76; P < .0001).
The global, open-label, phase 3 study enrolled patients with inoperable or metastatic hormone receptor–positive, HER2-negative breast cancer who received 1 or 2 prior lines of chemotherapy in the inoperable or metastatic setting. They were at least 18 years of age and had an ECOG performance status of 0 or 1. Notably, those with stable brain metastases were permitted, but those who had prior exposure to a chemotherapy agent targeting topoisomerase I, including ADCs, or a prior TROP2-targeted therapy were not.
Study participants were randomized 1:1 to receive datopotamab deruxtecan at 6 mg/kg given intravenously (IV) and once every 3 weeks (Q3W) or single-agent chemotherapy per investigator choice. Those in the control arm could have received IV eribulin at 1.4 mg/m2 on days 1 and 8 Q3W, oral capecitabine at 1000 mg/m2 or 1250 mg/m2 twice daily on days 1 to 14 Q3W, IV vinorelbine at 25 mg/m2 on days 1 and 8 Q3W, or IV gemcitabine at 1000 mg/m2 on days 1 and 8 Q3W.
They were stratified by number of prior lines of chemotherapy (1 vs 2), geographic region (United States/Canada/Europe vs other regions of the world), and prior exposure to a CDK4/6 inhibitor (yes vs no). Treatment continued until radiologic progression was confirmed by investigator assessment and RECIST 1.1 criteria, intolerable toxicity, withdrawn consent, or other discontinuation criteria were met.
The dual primary end points of the study were PFS by BICR and RECIST criteria and overall survival (OS). Key secondary end points included investigator-assessed PFS, objective response rate (ORR), 12-week disease control rate (DCR), duration of response (DOR), time to first subsequent therapy or death (TFST), time to second subsequent therapy or death (TSST), and time to second progression or death (PFS2). Safety was also examined.
CHMP summary of positive opinion for Datroway
Earlier this month, the FDA approved datopotamab deruxtecan-dlnk (Datroway) for use in adult patients with unresectable or metastatic, hormone receptor–positive, HER2-negative breast cancer who had prior exposure to endocrine-based therapy and chemotherapy for unresectable or metastatic disease.